| Added by | standudu |
|---|---|
| Group name | EquipeCTCS |
| Item Type | Journal Article |
| Title | ERR? promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors |
| Creator | Vargas et al. |
| Author | G. Vargas |
| Author | M. Bouchet |
| Author | L. Bouazza |
| Author | P. Reboul |
| Author | C. Boyault |
| Author | M. Gervais |
| Author | C. Kan |
| Author | C. Benetollo |
| Author | M. Brevet |
| Author | M. Croset |
| Author | M. Mazel |
| Author | L. Cayrefourcq |
| Author | S. Geraci |
| Author | S. Vacher |
| Author | F. Pantano |
| Author | M. Filipits |
| Author | K. Driouch |
| Author | I. Bieche |
| Author | M. Gnant |
| Author | W. Jacot |
| Author | J. E. Aubin |
| Author | M. Duterque-Coquillaud |
| Author | C. Alix-Panabières |
| Author | P. Clézardin |
| Author | E. Bonnelye |
| Abstract | Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERR?) has been implicated in cancer cell invasiveness. Here, we established that ERR? promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERR? expression levels were associated with bone but not lung metastases. ERR? expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERR? overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERR? expression level. In vivo, Rank was identified as a target for ERR?. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERR? reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERR?/RANK in breast cancer patients and also revealed a positive correlation between ERR? and BRCA1mut carriers. Taken together, our results reveal a novel ERR?/RANK axis by which ERR? in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERR? may be a useful therapeutic target to prevent bone metastases. |
| Publication | Oncogene |
| Volume | 38 |
| Issue | 7 |
| Pages | 950-964 |
| Date | 02 2019 |
| Journal Abbr | Oncogene |
| Language | eng |
| DOI | 10.1038/s41388-018-0579-3 |
| ISSN | 1476-5594 |
| Library Catalog | PubMed |
| Extra | PMID: 30478447 |
| Tags | Animals, Bone Neoplasms, Breast Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Mammary Neoplasms, Animal, Mice, Mice, Inbred BALB C, Neoplasm Proteins, original, Receptor Activator of Nuclear Factor-kappa B, Receptors, Estrogen |
| Date Added | 2019/05/14 - 17:46:09 |
| Date Modified | 2022/08/01 - 16:02:40 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
